视黄醇结合蛋白4作为2型糖尿病患者肾功能不全和心血管疾病的血浆生物标志物

Retinol-binding protein 4 as a plasma biomarker of renal dysfunction and cardiovascular disease in type 2 diabetes.

作者信息

Cabré A, Lázaro I, Girona J, Manzanares J, Marimón F, Plana N, Heras M, Masana L

机构信息

Department of Internal Medicine, Research Unit on Lipids and Atherosclerosis, Faculty of Medicine and Health Sciences, IRCIS, Sant Joan University Hospital, Reus, Spain.

出版信息

J Intern Med. 2007 Oct;262(4):496-503. doi: 10.1111/j.1365-2796.2007.01849.x.

DOI:10.1111/j.1365-2796.2007.01849.x

PMID:17875187

Abstract

OBJECTIVE

The retinol-binding protein 4 (RBP4) has been linked to the insulin resistance state in obesity and type 2 diabetes in animal studies. Data in humans are controversial and their relationship with organ damage in diabetic patients is lacking. We studied the association of plasma RBP4 with organ complications in type 2 diabetic patients.

SETTING

Sant Joan University Hospital, Reus, Spain.

SUBJECTS

165 nonsmoker type 2 diabetic subjects according to American Diabetes Association criteria, aged 36-79 years, without proteinuria or severely decreased glomerular filtration rates (MDRD-GFR <30 mL min(-1) 1.73 m(-2)), were included in the study.

MAIN OUTCOME MEASURE

Plasma RBP4 concentrations were the primary outcome variable. Statistics were performed in relation to clinical and subclinical arteriosclerosis, renal function parameters and biochemical data.

RESULTS

Plasma RBP4 concentrations were positively correlated with serum creatinine levels (r = 0.322, P < 0.001) and inversely correlated with MDRD-GFR (r = -0.468, P = 0.009). Patients with moderately renal dysfunction (MDRD-GFR <60 mL min(-1) 1.73 m(-2)) had higher plasma RBP4 concentrations than those with normal to mildly decreased GFR (55.3 +/- 24.6 vs. 40.8 +/- 15.4, P <0.001). Patients in the top quartile of RBP4 concentrations had an increased adjusted odds ratio for moderately renal dysfunction compared with lower quartiles (4.68; 95% CI: 1.52-14.36, P = 0.007). The presence of microalbuminuria was not associated with RBP4. Plasma RBP4 concentrations were higher in those subjects with previous clinical arteriosclerosis than in event-free subjects (48.8 +/- 24.2 vs. 40.6 +/- 13.9, P = 0.045). The presence of retinopathy or polyneuropathy did not differ across RBP4 quartiles.

CONCLUSIONS

Plasma RBP4 concentration might be a biomarker of nephropathy and cardiovascular disease in type 2 diabetic subjects.

摘要

目的

在动物研究中，视黄醇结合蛋白4（RBP4）与肥胖及2型糖尿病中的胰岛素抵抗状态相关。人体研究数据存在争议，且缺乏其与糖尿病患者器官损害关系的研究。我们研究了2型糖尿病患者血浆RBP4与器官并发症之间的关联。

研究地点

西班牙雷乌斯市圣琼大学医院。

研究对象

根据美国糖尿病协会标准纳入165例非吸烟的2型糖尿病患者，年龄36 - 79岁，无蛋白尿或肾小球滤过率严重降低（MDRD - GFR <30 mL·min⁻¹·1.73 m⁻²）。

主要观察指标

血浆RBP4浓度是主要观察变量。针对临床和亚临床动脉硬化、肾功能参数及生化数据进行统计分析。

结果

血浆RBP4浓度与血清肌酐水平呈正相关（r = 0.322，P < 0.001），与MDRD - GFR呈负相关（r = -0.468，P = 0.009）。中度肾功能不全（MDRD - GFR <60 mL·min⁻¹·1.73 m⁻²）患者的血浆RBP4浓度高于肾小球滤过率正常至轻度降低的患者（55.3 ± 24.6 vs. 40.8 ± 15.4，P <0.001）。与RBP4浓度最低四分位数的患者相比，RBP4浓度最高四分位数的患者中度肾功能不全的校正比值比升高（4.68；95% CI：1.52 - 14.36，P = 0.007）。微量白蛋白尿的存在与RBP4无关。既往有临床动脉硬化的患者血浆RBP4浓度高于无此情况的患者（48.8 ± 24.2 vs. 40.6 ± 13.9，P = 0.045）。视网膜病变或多发性神经病变的存在在RBP4四分位数间无差异。